Immune and inflammatory responses in TNF alpha-deficient mice: A critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response
Author(s)
Pasparakis, M
Alexopoulou, L
Episkopou, V
Kollias, G
Type
Journal Article
Abstract
To investigate the role of TNF alpha in the development of in vivo immune response we have generated TNF alpha-deficient mice by gene targeting. Homozygous mutant mice are viable and fertile, develop lymph nodes and Peyer's patches and show no apparent phenotypic abnormalities, indicating that TNF alpha is not required for normal mouse development. In the absence of TNF alpha mice readily succumb to L. monocytogenes infections and show reduced contact hypersensitivity responses. Furthermore, TNF alpha knockout mice are resistant to the systemic toxicity of LPS upon D-galactosamine sensitization, yet they remain sensitive to high doses of LPS alone. Most interestingly, TNF alpha knockout mice completely lack splenic primary B cell follicles and cannot form organized follicular dendritic cell (FDC) networks and germinal centers. However, despite the absence of B cell follicles, Ig class-switching can still occur, yet deregulated humoral immune responses against either thymus-dependent (TD) or thymus-independent (TI) antigens are observed. Complementation of TNF alpha functioning by the expression of either human or murine TNF alpha transgenes is sufficient to reconstitute these defects, establishing a physiological role for TNF alpha in regulating the development and organization of splenic follicular architecture and in the maturation of the humoral immune response.
Date Issued
1996-10-01
Date Acceptance
1996-10-01
Citation
Journal of Experimental Medicine, 1996, 184 (4), pp.1397-1411
ISSN
0022-1007
Publisher
Rockefeller University Press
Start Page
1397
End Page
1411
Journal / Book Title
Journal of Experimental Medicine
Volume
184
Issue
4
Copyright Statement
©The Rockefeller University Press
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1996VP23000023&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
TUMOR-NECROSIS-FACTOR
DRAINING LYMPH-NODES
FACTOR RECEPTOR
LISTERIA-MONOCYTOGENES
ENDOTOXIC-SHOCK
CONTACT HYPERSENSITIVITY
TRANSMEMBRANE FORM
LYMPHOTOXIN-BETA
LYMPHOCYTES-B
T-CELLS
Publication Status
Published